POS0462 HYDROXYCHLOROQUINE REDUCES THE TITERS OF ANTI-DOMAIN 1 ANTIBODIES OVER TIME IN PATIENTS WITH PERSISTENTLY POSITIVE ANTIPHOSPHOLIPID ANTIBODIES: RESULTS FROM THE APS ACTION CLINICAL DATABASE AND REPOSITORY (“REGISTRY”)
Authors: C. Chighizola, F. Pregnolato, D. Andrade, M. Tektonidou, S. Sciascia, V. Pengo, A. Ugarte, H. M. Belmont, M. Gerosa, P. Fortin, C. Lopez-Pedrera, Z. Zhang, T. Atsumi, G. De Jesùs, N. Kello, D. W. Branch, L. Andreoli, D. Wahl, M. A. Petri, E. Rodríguez Almaraz, R. Cervera, G. Pons Estel, J. Knight, R. Willis, M. Barber, B. Artim Esen, M. Efthymiou, D. Erkan, M. L. Bertolaccini
Journal: Annals of the Rheumatic Diseases (2022)

Background Data on fluctuation of antibodies directed against domain 1 (anti-D1) of β 2 -glycoprotein I (β 2 GPI) are scarce. Patients with antiphospholipid syndrome (APS) and all three criteria tests for antiphospholipid antibodies (aPL) display higher titers of anti-D1, which correlate with anti-β 2 GPI levels. Objectives This project aims at evaluating predictors of the variation of anti-D1 titers over time in a large international cohort of persistently aPL positive patients. Methods AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Registry was created to study the course of persistently aPL-positive patients with or without autoimmune disorders over at least 10 years. Inclusion criteria are positive aPL by Updated Sapporo Criteria tested within one year prior to enrolment. Patients are followed every 12±3 months with clinical data and blood collection. Patients with available blood samples from at least three time points were included in this analysis. Anti-β 2 GPI and anti-D1 IgG were tested by chemiluminescence (BioFlash, Werfen) at APS ACTION core laboratories. Positive results were defined as &gt;20 CU, according to the manufacturer. Clinical data were retrieved from APS ACTION online database. Anti-D1 titers within the same subject were compared by Friedman’s test. A mixed linear model was built to identify predictors of the fluctuation of anti-D1 antibody titers over time. Results In this longitudinal study, 230 patients with anti-D1 tested at 4 time points were included (Table 1). Patients with thrombotic APS had anti-D1 titers significantly higher than those without thrombosis (p=0.022). Among 135 patients with at least one anti-D1 positive result, anti-D1 titers varied significantly over time (Friedman statistics: 508.5, p&lt;0.0001; anti-D1 geometric mean at baseline 189.0; T1 132.3 [-15%]; T2 113.8 [-17%]; T3 109.2 [-6% versus T2, -38% versus T1]). Anti-D1 titers were significantly higher at baseline compared to T3 (p=0.029). In the 4 years of follow-up, 18 new thrombotic events occurred. Patients with double/triple aPL positivity displayed 12.5 fold increase [95%CI 7.4-20.0] in baseline anti-D1 titers. After adjustment for age, gender and number of positive aPL tests, the fluctuation of anti-D1 titers was associated with treatment with hydroxychloroquine (HCQ) at each time-point. In particular, treatment with HCQ, but not those with conventional immunosuppressors, was associated with a 1.3-fold decrease in anti-D1 titers [95%CI 1.1-1.5]. In the same multivariable model, incident vascular events were associated with a 1.5 fold increase of anti-D1 titers. A concomitant diagnosis of systemic lupus erythematosus did not affect the fluctuation of anti-D1 titers. Table 1. Demographic and Clinical Characteristics of 230 APS ACTION Registry Patients with anti-D1 tested ≥3 time points during the follow-up Anti-D1 pos samples Anti-D1 neg samples p-value Overall sample (n=135) (n=95) (n=230) Age [years] mean (SD ) 42.3 (11.8) 48.8 (13.0) 0.0001 45.0 (12.7) %Female (n ) 71.9 (97) 65.3 (62) 0.358 69.1 (159) Associated systemic autoimmune disease 39.3 (53) 44.2 (42) 0.539 41.3 (95) aPL without APS 19.3 (26) 34.7 (33) 0.010 25.7 (59) Thrombotic APS 54.1 (73) 53.7 (51) 53.9 (124) Obstetric APS 11.9 (16) 5.3 (5) 9.1 (21) Thrombotic/+obstetric APS 14.8 (20) 6.3 (6) 11.3 (26) aCL IgG 89.5 (119/133) 25.5 (24/94) &lt;0.0001 63.0 (143/227) aCL, IgM 36.1 (48/133) 27.7 (26/94) 0.234 32.6 (74/227) Anti-2GPI, IgG 93.2 (124/133) 39.4 (37/94) &lt;0.0001 70.9 (161/227) Anti-2GPI, IgM 34.6 (46/133) 21.3 (20/94) 0.043 29.1 (66/227) LA 82.8 (82/99) 59.5 (44/74) 0.001 72.8 (126/173) Conclusion Treatment with HCQ and vascular events during follow-up were identified as significant predictors of the fluctuation of anti-D1 antibody titers over time. Disclosure of Interests None declared.